Roflupram exerts neuroprotection via activation of CREB/PGC‐1α signalling in experimental models of Parkinson's disease

• DOI: 10.1111/bph.14983
• Publication Date: 2020-01-24T00:45:05Z
• Authors: Jiahong Zhong; Wenli Dong; Yunyun Qin; Jinfeng Xie; Jiao Xiao; Jiangping Xu; Haitao Wang
• Keywords: MPTP

Background and Purpose Roflupram improves cognition limits neuroinflammation in the brain. However, beneficial effects of roflupram on Parkinson's disease (PD) remain unknown. Therefore, we aimed to elucidate pharmacological mechanisms action ROF experimental models PD. Experimental Approach We used an vitro PD model SH‐SY5Y cells exposed 1‐methyl‐4‐phenylpyridinium iodide (MPP + ). Cell viability apoptosis were analysed via MTT assay flow cytometry. Mitochondrial morphology, mitochondrial respiratory capacity, ROS measured by a tracker, Seahorse Analyzer, MitoSOX‐Red dye. For vivo model, behavioural tests, Nissl staining, immunohistochemistry evaluate protection roflupram. The levels TH, cAMP response element‐binding protein (CREB), PPARγ coactivator‐1α (PGC‐1α) western blotting. Key Results decreased MPP ‐induced human dopaminergic neurons. also increased production, restored morphology. reversed reductions phosphorylated CREB, PGC‐1α TH. These protective blocked PKA inhibitor H‐89 or siRNA. In mice treated with MPTP, significantly improved motor functions. prevented both neuronal loss reduction CREB substantia nigra striatum. Conclusion Implications protected neurons from CREB/PGC‐1α pathway models. Hence, has potential as drug treatment